Potential Effects of Naringenin on Hepatic Lipid Accumulation and Lipogenesis-Related Gene Expression in High-Fat Diet-Fed Rats
- 1Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia
- 2College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia
Abstract
This study investigated the protective effects of naringenin (NAR) against metabolic dysfunction-associated steatotic liver disease (MASLD) in male Wistar rats fed a high-fat diet (HFD). We fed rats a high-fat diet for a total of 12 weeks, with oral NAR administered daily from weeks 9–12 (n = 8 rats/group). The HFD group (from week 9) were divided into four experimental groups: HFD (control); HFD+ 50 mg/kg NAR; HFD+ 100 mg/kg NAR; and HFD+ 200 mg/kg NAR. In addition, rats receiving standard diet (from week 9) were divided into two groups: a normal control (NC) group (i.e., standard diet + vehicle) and an NC+ 200 mg/kg NAR. NAR was orally administered for the last 4 weeks. We observed that the increasing doses (100 and 200 mg/kg) of NAR decreased body mass index (BMI), liver function markers, fasting plasma glucose and insulin, and HOMA-IR, and improved hepatic and serum lipid profiles. At 200 mg/kg, NAR reduced body weight by about 20.4%, BMI by 19.2%, serum ALT by 24%, AST by 43%, fasting glucose by 21%, fasting insulin by 44%, HOMA-IR by 56%, serum TG by 37%, TC by 41%, and LDL-c by 25%, and it increased HDL-c by 20%, relative to the HFD group. Similarly, it lowered the hepatic TG by 35.1%, TC by 28.4%, and LDL-C by 30.3%, while raising HDL-C by 31.8%. Histopathological examination of the liver revealed enhanced hepatocellular structure, reduced cytoplasmic vacuolation, decreased immune cell infiltration, and reduced injury scores. Furthermore, NAR was associated with improved antioxidant status, demonstrated by increasing the levels antioxidant mediators such as mRNA Nrf2, GSH, GSH-Px, SOD, and CAT in the liver. Moreover, it suppressed inflammatory mediators, including TNF-α, IL-1β, IL-6, and mRNA NF-κB, while elevating the anti-inflammatory cytokine IL-10. NAR was associated with increased hepatic SIRT1 and decreased PPARγ, ChREBP, and SREBP-1c mRNA levels. The more pronounced effect of NAR was observed at 200 mg/kg. These results of our study suggest the potential of NAR as a therapeutic candidate for MASLD, improving metabolic parameters and reducing hepatic lipid accumulation and inflammation associated with MASLD- like model, alongside improved antioxidant status and changes in SIRT1 and ChREBP/SREBP-1c expression.
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BibTeX
@article{alshehri2026potential,
title = {{Potential Effects of Naringenin on Hepatic Lipid Accumulation and Lipogenesis-Related Gene Expression in High-Fat Diet-Fed Rats}},
author = {Sarah Ahmed Alshehri and Magdi A. Osman and Ghada Alnafisah and Shaheerah Asiri and Shaista Arzoo and Laila Naif Al-Harbi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219453},
url = {https://www.mdpi.com/1422-0067/27/21/9453},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Potential Effects of Naringenin on Hepatic Lipid Accumulation and Lipogenesis-Related Gene Expression in High-Fat Diet-Fed Rats
AU - Sarah Ahmed Alshehri
AU - Magdi A. Osman
AU - Ghada Alnafisah
AU - Shaheerah Asiri
AU - Shaista Arzoo
AU - Laila Naif Al-Harbi
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219453
UR - https://www.mdpi.com/1422-0067/27/21/9453
AB - This study investigated the protective effects of naringenin (NAR) against metabolic dysfunction-associated steatotic liver disease (MASLD) in male Wistar rats fed a high-fat diet (HFD). We fed rats a high-fat diet for a total of 12 weeks, with oral NAR administered daily from weeks 9–12 (n = 8 rats/group). The HFD group (from week 9) were divided into four experimental groups: HFD (control); HFD+ 50 mg/kg NAR; HFD+ 100 mg/kg NAR; and HFD+ 200 mg/kg NAR. In addition, rats receiving standard diet (from week 9) were divided into two groups: a normal control (NC) group (i.e., standard diet + vehicle) and an NC+ 200 mg/kg NAR. NAR was orally administered for the last 4 weeks. We observed that the increasing doses (100 and 200 mg/kg) of NAR decreased body mass index (BMI), liver function markers, fasting plasma glucose and insulin, and HOMA-IR, and improved hepatic and serum lipid profiles. At 200 mg/kg, NAR reduced body weight by about 20.4%, BMI by 19.2%, serum ALT by 24%, AST by 43%, fasting glucose by 21%, fasting insulin by 44%, HOMA-IR by 56%, serum TG by 37%, TC by 41%, and LDL-c by 25%, and it increased HDL-c by 20%, relative to the HFD group. Similarly, it lowered the hepatic TG by 35.1%, TC by 28.4%, and LDL-C by 30.3%, while raising HDL-C by 31.8%. Histopathological examination of the liver revealed enhanced hepatocellular structure, reduced cytoplasmic vacuolation, decreased immune cell infiltration, and reduced injury scores. Furthermore, NAR was associated with improved antioxidant status, demonstrated by increasing the levels antioxidant mediators such as mRNA Nrf2, GSH, GSH-Px, SOD, and CAT in the liver. Moreover, it suppressed inflammatory mediators, including TNF-α, IL-1β, IL-6, and mRNA NF-κB, while elevating the anti-inflammatory cytokine IL-10. NAR was associated with increased hepatic SIRT1 and decreased PPARγ, ChREBP, and SREBP-1c mRNA levels. The more pronounced effect of NAR was observed at 200 mg/kg. These results of our study suggest the potential of NAR as a therapeutic candidate for MASLD, improving metabolic parameters and reducing hepatic lipid accumulation and inflammation associated with MASLD- like model, alongside improved antioxidant status and changes in SIRT1 and ChREBP/SREBP-1c expression.
SN - 1422-0067
ER -